scholarly journals Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 540-552 ◽  
Author(s):  
Hany H. Arab ◽  
Samir A. Salama ◽  
Tamer M. Abdelghany ◽  
Hany A. Omar ◽  
El-Shaimaa A. Arafa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mapk Pathway ◽  
Lipid Peroxide ◽  
Mitogen Activated Protein Kinase ◽  
Camel Milk ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.

scholarly journals Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaochen Chen ◽  
Haofeng Lin ◽  
Jinyang Chen ◽  
Lisheng Wu ◽  
Junqing Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Mediator ◽  
Mapk Pathway ◽  
Bone Destruction ◽  
New Drugs ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Inflammatory Mediator Production ◽  
Tnf Α ◽  
Mitogen Activated Protein

Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1β, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.

scholarly journals Nerolidol: a potential approach in rheumatoid arthritis through reduction of TNF-α, IL-1β, IL-6, NF-Kβ, COX-2 and anti-oxidant effect in CFA-induced arthritic model

2021 ◽  
Author(s):  
Shanila Akhter ◽  
Hafiz Muhammad Irfan ◽  
Alamgeer Yuchi ◽  
Shah Jahan ◽  
Muhammad Shahzad ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Body Weight ◽  
Inflammatory Cytokines ◽  
The Body ◽  
Primary Study ◽  
Tnf Α ◽  
Ankle Joints ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Abstract Rheumatoid arthritis an autoimmune infectious disorder, is categorized by inflammation and increased level of pro-inflammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic inflammation. On the basis of established anti-inflammatory efficacy of Nerolidol, the primary study was further appraised to determine its efficacy against Freund’s complete adjuvant (CFA) rheumatoid model. Arthritis was persuaded by inoculation of 0.1mL CFA injection into left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radio-graphics of ankle joints. Expressions of cytokine’s panels like IL-10, IL-4, COX-2, NF-Kβ, TNF-α, IL-6, PGE-2 and IL-1β were determined by real time qPCR. Antioxidant enzyme analyses was calculated by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented the body weight loss, stabilized the biochemical and haematological homeostasis and significantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, over expression of gene pointers like TNF-α, IL-1β, IL-6, NF-Kβ, PGE-2 and COX-2 in CFA treated control rats were also reversed with nerolidol. This anti-arthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum anti-oxidant activity. The present findings demonstrate that nerolidol reduce the adjuvant arthritis by down-regulating the proinflammatory cytokines and up-regulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.

scholarly journals Processed Scutellaria baicalensis Georgi Extract Alleviates LPS-Induced Inflammatory and Oxidative Stress through a Crosstalk between NF-κB and KEAP1/NRF2 Signaling in Macrophage Cells

2021 ◽  
Vol 11 (13) ◽  
pp. 6055
Author(s):  
Akhtar Ali ◽  
En-Hyung Kim ◽  
Jong-Hyun Lee ◽  
Kang-Hyun Leem ◽  
Shin Seong ◽  
...  
Keyword(s):  
Scutellaria Baicalensis ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Scutellaria Baicalensis Georgi ◽  
Anticancer Effects ◽  
Tnf Α ◽  
Clinical Benefits ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Prolonged inflammation results in chronic diseases that can be associated with a range of factors. Medicinal plants and herbs provide synergistic benefits based on the interaction of multiple phytochemicals. The dried root of Scutellaria baicalensis Georgi and its compounds possess anti-inflammatory, anti-oxidative, and anticancer effects. Processing is a traditional method to achieve clinical benefits by improving therapeutic efficacy and lowering toxicity. In this study, we investigated the anti-inflammatory and anti-oxidant effect of processed Scutellaria baicalensis Georgi extract (PSGE) against lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Data using Griess assay and ELISA showed that PSGE decreased nitric oxide and prostaglandin E2 (PGE2) levels against LPS. PSGE treatment up-regulated 15-hydroxyprostaglandin dehydrogenase (PGDH), while cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 expression did not change. Interestingly, PGE2 inhibition was regulated by prostaglandin catabolic enzyme 15-PGDH rather than COX-2/mPGES-1, enzymes essential for PGE2 synthesis. Additionally, PSGE-suppressed LPS-induced IL-6 and TNF-α production through NF-κB signaling. NF-κB release from an inactive complex was inhibited by HO-1 which blocked IκBα phosphorylation. The ROS levels lowered by PSGE were measured with the H2DCFDA probe. PSGE activated NRF2 signaling and increased antioxidant Hmox1, Nqo1, and Txn1 gene expression, while reducing KEAP1 expression. In addition, pharmacological inhibition of HO-1 confirmed that the antioxidant enzyme induction by PSGE was responsible for ROS reduction. In conclusion, PSGE demonstrated anti-inflammatory and anti-oxidant effects due to NRF2/HO-1-mediated NF-κB and ROS inhibition.

IGF-I and insulin amplify IL-1β-induced nitric oxide and prostaglandin biosynthesis

1998 ◽  
Vol 274 (4) ◽  
pp. F673-F679 ◽  
Author(s):  
Zhonghong Guan ◽  
Shaavhree Y. Buckman ◽  
Lisa D. Baier ◽  
Aubrey R. Morrison
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
No Production ◽  
Glomerular Mesangial Cells ◽  
Igf I ◽  
Mitogen Activated Protein ◽  
Transduction Mechanisms ◽  
Cox 2

The inflammatory cytokine interleukin-1β (IL-1β) induces both cyclooxygenase-2 (Cox-2) and the inducible nitric oxide synthase (iNOS) with concomitant release of PGs and nitric oxide (NO) by glomerular mesangial cells. In our current studies, we determine whether insulin and IGF-I are involved in the signal transduction mechanisms resulting in IL-1β-induced NO and PGE2biosynthesis in renal mesangial cells. We demonstrate that both insulin and IGF-I increase IL-1β-induced Cox-2 and iNOS protein expression, which in turn enhance PGE2 and NO production. Our data also indicate that both insulin and IGF-I enhance IL-1β-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation and SAPK activation. These findings implicate the possible role of the MAPK pathway in mediating the effects of insulin and IGF-I on the upregulation of cytokine-stimulated NO and PG biosynthesis. Together, our results indicate that IGF-I and insulin may function to modulate the renal inflammatory process.

Neisseria meningitidis-mediates proinflammatory responses in PMN: Crosstalk TLR-2/c-JunN-Terminal

2018 ◽  
Vol 6 (4) ◽  
pp. 362-378
Author(s):  
Yanyan Xu ◽  
Hanan Slimani
Keyword(s):  
Neisseria Meningitidis ◽  
Mapk Pathway ◽  
Nuclear Factor Κb ◽  
Primary Response ◽  
Mitogen Activated Protein Kinase ◽  
Murine Bone Marrow ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Proinflammatory Responses ◽  
Meningitis In Children

Neisseria meningitidis is a Gram-negative bacterium emerging the leading cause of bacterial meningitis in children and young adult wide world. The host innate immune response against meningitis is largely unknown. In this study, we show that N.meningitidis robustly activates mRNA and protein expression of tumor necrosis factor (TNF-α) and interleukin (IL-6) in murine bone marrow-derived PMN. Toll-like receptor (TLR-2) and myeloid differentiation primary response gene 88 (MyD88), N.meningitidis also activates the mitogen-activated protein kinase (MAPKs; c-Jun N-terminal kinase (JNK), ERK1/2 and p38 MAPK) pathway. N.meningitidis-induced TNF-α and IL-6 production was dependent on JNK activation. The intracellular reactive oxygen species (ROS), NADPH oxidase-2, and nuclear factor-κB are required for N.meningitides-induced proinflammatory cytokine generation in PMN. Together, we have demonstrated that N.meningitidis-induced activation of host proinflammatory cytokines is mediated through TLR2-dependent JNK signaling pathways.

scholarly journals Could Polyphenols Help in the Control of Rheumatoid Arthritis?

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1589 ◽  
Author(s):  
Sung ◽  
Kwon ◽  
Um ◽  
Kim
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Mitogen Activated Protein Kinase ◽  
Bone Damage ◽  
Autoimmune Inflammatory Disease ◽  
Novel Drugs ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Factor Α ◽  
Therapeutic Alternatives

Rheumatoid arthritis (RA) is a chronic, systemic, joint-invading, autoimmune inflammatory disease, which causes joint cartilage breakdown and bone damage, resulting in functional impairment and deformation of the joints. The percentage of RA patients has been rising and RA represents a substantial burden for patients around the world. Despite the development of many RA therapies, because of the side effects and low effectiveness of conventional drugs, patients still need and researchers are seeking new therapeutic alternatives. Polyphenols extracted from natural products are effective on several inflammatory diseases, including RA. In this review polyphenols are classified into four types: flavonoids, phenolic acids, stilbenes and others, among which mainly flavonoids are discussed. Researchers have reported that anti-RA efficacies of polyphenols are based mainly on three mechanisms: their anti-inflammatory, antioxidant and apoptotic properties. The main RA factors modified by polyphenols are mitogen-activated protein kinase (MAPK), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor κ light chain enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinases (JNK). Polyphenols could be potent alternative RA therapies and sources for novel drugs for RA by affecting its key mechanisms.

scholarly journals δ-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated Macrophages

2018 ◽  
Vol 19 (10) ◽  
pp. 3022 ◽  
Author(s):  
Junjun Shen ◽  
Tao Yang ◽  
Youzhi Xu ◽  
Yi Luo ◽  
Xinyue Zhong ◽  
...  
Keyword(s):  
Rice Bran ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Activator Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Inflammatory Effect

δ-Tocotrienol, an important component of vitamin E, has been reported to possess some physiological functions, such as anticancer and anti-inflammation, however their molecular mechanisms are not clear. In this study, δ-tocotrienol was isolated and purified from rice bran. The anti-inflammatory effect and mechanism of δ-tocotrienol against lipopolysaccharides (LPS) activated pro-inflammatory mediator expressions in RAW264.7 cells were investigated. Results showed that δ-tocotrienol significantly inhibited LPS-stimulated nitric oxide (NO) and proinflammatory cytokine (TNF-α, IFN-γ, IL-1β and IL-6) production and blocked the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 (ERK1/2). δ-Tocotrienol repressed the transcriptional activations and translocations of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), which were closely related with downregulated cytokine expressions. Meanwhile, δ-tocotrienol also affected the PPAR signal pathway and exerted an anti-inflammatory effect. Taken together, our data showed that δ-tocotrienol inhibited inflammation via mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor (PPAR) signalings in LPS-stimulated macrophages.

scholarly journals NF-κB-dependent anti-inflammatory activity of urolithins, gut microbiota ellagic acid-derived metabolites, in human colonic fibroblasts

2010 ◽  
Vol 104 (4) ◽  
pp. 503-512 ◽  
Author(s):  
Antonio González-Sarrías ◽  
Mar Larrosa ◽  
Francisco Abraham Tomás-Barberán ◽  
Piero Dolara ◽  
Juan Carlos Espín
Keyword(s):  
Gut Microbiota ◽  
Ellagic Acid ◽  
Mitogen Activated Protein Kinase ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
The Individual

Previous studies have reported the anti-inflammatory properties of pomegranate extracts, suggesting that ellagitannins (ET) and ellagic acid (EA) are the main anti-inflammatory compounds. However, both ET and EA are metabolised in vivo by the gut microbiota to yield urolithins (Uro) which can be found in the gut and in systemic bloodstream. The present study was carried out to evaluate the individual effect of EA and their microbiota-derived metabolites Uro on colon fibroblasts upon IL-1β treatment as an in vitro inflammation model. Uro-A and Uro-B (10 μm) inhibited PGE2 production (85 and 40 %, respectively) after IL-1β stimulation, whereas EA did not show any effect. Uro-A, but not Uro-B, down-regulated cyclo-oxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) mRNA expression and protein levels. Both Uro inhibited NF-κB translocation to nucleus. Slight but significant effects were found in the activation of mitogen-activated protein kinase (MAPK) pathways. Uro-A lowered c-Jun N-terminal kinase phosphorylation state, and both Uro inhibited p38 activation. No metabolites derived from Uro or EA were found in the cell media upon incubation of EA or Uro with the cells, and only traces of the compounds were found inside the cells. The present results suggest that Uro, mainly Uro-A, are the main compounds that are responsible for the pomegranate anti-inflammatory properties. The mechanism of action implicated seems to be via the inhibition of activation of NF-κB and MAPK, down-regulation of COX-2 and mPGES-1 expressions, and consequently,via the reduction of PGE2 production. Taking into account that Uro did not enter the cells, a competitive binding for IL-1β membrane receptor cannot be discarded.

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